The
estrogen receptor (ER) is a target for endocrine
therapy in
breast cancer patients. Individual quantification of ERα and ERβ expression, rather than total ER levels, might enable better prediction of the response to treatment. We recently developed the tracer
2-18F-fluoro-6-(6-hydroxynaphthalen-2-yl)pyridin-3-ol (18F-FHNP) for assessment of ERβ levels with PET. In the current study, we investigated several pharmacokinetic analysis methods to quantify changes in ERβ availability with
18F-FHNP PET. Methods: Male nude rats were subcutaneously inoculated in the shoulder with ERα/ERβ-expressing SKOV3 human
ovarian cancer cells. Two weeks after
tumor inoculation, a dynamic
18F-FHNP PET scan with arterial blood sampling was acquired from rats treated with vehicle or various concentrations of
estradiol (nonspecific ER agonist) or
genistein (ERβ-selective agonist). Different pharmacokinetic models were applied to quantify ERβ availability in the
tumor. Results: Irreversible-uptake compartmental models fitted the kinetics of
18F-FHNP uptake better than reversible models. The irreversible 3-tissue-compartment model, which included both the parent and the metabolite input function, gave results comparable to those of the irreversible 2-tissue-compartment model with only a parent input function, indicating that radioactive metabolites contributed little to the
tumor uptake. Patlak graphical analysis gave metabolic rates (Ki, the irreversible uptake rate constant) comparable to compartment modeling. The Ki values correlated well with ERβ expression but not with ERα, confirming that Ki is a suitable parameter to quantify ERβ expression. SUVs at 60 min after tracer injection also correlated (r2 = 0.47; P = 0.04) with ERβ expression. A reduction in
18F-FHNP tumor uptake and Ki values was observed in the presence of
estradiol or
genistein. Conclusion:18F-FHNP PET enables assessment of ERβ availability in
tumor-bearing rats. The most suitable parameter to quantify ERβ expression is the Ki However, a simplified static imaging protocol for determining the SUVs can be applied to assess ERβ levels.